| Objective: To observe the effect of Taohongsiwu Decoction(THSWD)on blood pressure,hemorheology,endothelium-dependent relaxation function,endotheliumrelated factors and ATF4/CHOP pathway gene expression of endoplasmic reticulum stress in spontaneously hypertensive rats(SHR),and to study the mechanism of promoting blood circulation(huoxuehuayu)method in treating hypertension and protecting vascular endothelial cells.Methods: 24 ten week old male SHRs were randomly divided into model group,the medium dose THSWD group,the high dose THSWD group and Losartan group,6 rats in each group;6 ten week old male WKY rats were normal control group,and the dosage of THSWD and Losartan was converted according to the body surface area of human rats,and the intervention was given by gavage for 10 days.Bp-2000 noninvasive blood pressure analyzer was used to detect the blood pressure changes during the period,the endothelium-dependent diastolic function was recorded by in vitro vascular perfusion device,the hemorheology related indexes were detected by fullautomatic blood analysis;the levels of NO,ET-1,v WF,TM and EPCR in serum,the levels of t-PA and PAI in plasma were detected by Enzyme Linked Immuno Sorbent Assay(ELISA);Western blot method was used to detect the aorta protein expression of ATF4,CHOP,Bid,Bim,caspase-3,Bcl-2 and Bcl-x L.Results: 1.Blood pressure: After 10 days’ gavage,comparing with WKY group,the blood pressure of SHR group was higher(P < 0.05).Comparing with SHR group,the blood pressure of THSWD(9.18g/kg)group,THSWD(18.36g/kg)group and Losartan group decreased significantly(P < 0.05).2.Hemorheology: Comparing with WKY group,the results showed that the plasma viscosity,VSR3,VSR50 and VSR200 were higher in SHR group.Comparing with SHR group,the plasma viscosity,VSR3,VSR50,VSR200,hematocrit and erythrocyte aggregation index were lower in THSWD(9.18g/kg)group and THSWD(18.36g/kg)group(P < 0.05).Comparing with SHR group,the erythrocyte deformation index was higher(P < 0.05).the results of VSR50 and hematocrit were lower in Losartan group(P < 0.05).3.Endothelium dependent diastolic function: Comparing with WKY group,the maximum diastolic rate of SHR group decreased(P < 0.05).Comparing with SHR group,THSWD(9.18g/kg),THSWD(18.36g/kg)and Losartan group showed an increase in the maximum diastolic rate(P < 0.05).4.Endothelium related factors.Comparing with WKY group,the level of NO showed a decrease(P < 0.05),the level of ET-1,v WF,TM,EPCR and PAI-1 showed an increase(P < 0.05),and the level of t-PA showed no significant difference in SHR group(P > 0.05).Comparing with SHR group,the levels of NO and t-PA increased in THSWD(9.18g/kg),THSWD(18.36g/kg)and Losartan group,while the levels of ET-1,v WF,TM,EPCR and PAI-1 decreased in THSWD(9.18g/kg),THSWD(18.36g/kg)and Losartan group.THSWD(18.36g/kg)group was better than Losartan group in increasing NO level and decreasing PAI-1 level(P < 0.05).5.Endoplasmic reticulum stress and apoptosis related protein expression: Comparing with WKY group,the expression of ATF4,chop,BIM,bid and caspase-3 protein in SHR group showed an increase,while the expression of Bcl-2 and Bcl-x L protein showed a decrease(P < 0.05).Comparing with SHR group,the expression of ATF4,CHOP,Bim,Bid and caspase-3 protein in THSWD(9.18g/kg),THSWD(18.36g/kg)and Losartan group showed a decrease,while the expression of Bcl-2 and Bcl-x L protein showed an increase.THSWD(18.36g/kg)group was better than Losartan group in decreasing the expression of CHOP,Bim,Bid,caspase-3 protein and increasing the expression of Bcl-2 and Bclx L protein.Conclusion: 1.THSWD could reduce SHRs’ blood pressure,improve SHRs’ hemorheology,endothelium-dependent relaxation function and endothelium-derived related factor level.The protective effect of THSWD on VEC was further verified.2.The mechanism of THSWD protecting endothelial cells may be related to the regulation of expression of ATF4/CHOP pathway related proteins in endoplasmic reticulum stress,and inhibition of cell apoptosis. |
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